Systematic literature review of processes and challenges in establishing accurate diagnosis of hematologic malignancies

e17017 Background: Multiple tests are often needed to ensure accurate differential diagnosis (DDX) of hematologic malignancies, particularly for rare/complex conditions. Integration of morphology, immunophenotype, cytogenetic, and molecular results present challenges but is critical to determine prognostic parameters and treatment (tx) decisions. Methods: Systematic literature search was performed (PubMed/MedLine, EMBASE, Cochrane Library) for US-based articles in last 10 yrs regarding DDX of myelodysplastic syndrome, myeloproliferative neoplasm, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma. Results: 35 articles were identified that addressed methods (n=27) and/or accuracy/timing (n=15) of establishing a diagnosis. Diagnostic (dx) ability improved with use of systematic processes/algorithms (ALG), comparative techniques, and harmonization/central review; few ALG were comprehensive. Updates/revisions of disease-specific dx criteria could result in dx change. Accuracy improved with experienced clinicians (disease-specific knowledge), specialized pathologists (vs. generalists), tissue sample type/quality, and ancillary test availability. A pathologist’s dx ability was related to experience with rare/complex histological subtypes. Dx accuracy was often complicated by inconsistent/overlapping clinical presentation and lack of standardized terminology or reproducible results across facilities. Delays were attributed to lack of dx experience and patient’s health insurance type. Impact of dx delay on clinical outcomes was largely not addressed. Conclusions: With shift from morphologic- to genetic/molecular-based approaches, determination of tests done in parallel/reflexively often requires expert input. Impact of delayed dx on clinical outcomes is lacking. Standardized dx processes/ALG, along with access to expert hematopathologist review and interpretation of test results, may lead to earlier and improved dx accuracy and appropriate/timely tx initiation, thereby avoiding consequences of erroneous dx, especially of benign conditions initially dx as malignant.